Since linezolid, which is an oxazolidinone antibiotic, was first reported in 1984 (see European Patent Publication No. 127,902), a variety of oxazolidinone derivatives have been reported by various pharmaceutical firms. However, medicines under development do not have superior properties to linezolid (Product name: Zyvox) in terms of toxicity and efficacy. Due to such problems, linezolid is still drawing attention as the best alternative to vancomycin in treatment against methicillin-resistant staphylococcus aureus (MRSA). If linezolid-resistant bacteria, which have recently been reported, continue to spread, however, very serious problems, i.e., no cure for linezolid-resistant bacteria, occur.
For this reason, there is a very urgent need to develop medicines having superior properties to linezolid in terms of effects or toxicity and having efficacy for linezolid-resistant bacteria. Korean Patent Application No.: 10-2008-0093712, which was filed by the present inventors in Sep. 24, 2008, discloses that an oxazolidinone antibiotic having a cyclic amidrazone or cyclic amidoxime group has superior properties to linezolid in terms of efficacy and toxicity and the oxazolidinone antibiotic has various advantages due to introduction of the cyclic amidrazone group.
In particular, the cyclic amidrazone group is weakly basic and thus forms a salt. When the cyclic amidrazone group forms a hydrochloride, the hydrochloride has similar acidity to acetic acid, i.e., a pKa of about 5. Due to such weak acidity, antibacterial effects are not deteriorated and solubility of the hydrochloride with respect to water may be significantly increased.
However, the oxazolidinone antibiotic disclosed in the above-described patent application also has an insignificant effect on linezolid-resistant bacteria and thus cannot be used to effectively treat infections with linezolid-resistant bacteria under circumstances which the bacteria continue to spread.